Examine the effects of alpha particles on the overall genetic integrity of mammalian cells, to establish the minimal number of alpha particles necessary for the transformation of individual mammalian cells, and to identify and compare the genetic lesions (activation of oncogenes or inactivation of tumor suppressor genes) induced in these transformants. To date, a genetic signature for mammalian cells that have been transformed by ionizing radiation has yet to be determined. The results generated from these proposed studies will provide important clues into defining the mutational spectrum induced by single, or multiple alpha particles in mammalian cells at the DNA level, and how these mutations lead to cellular transformation.